Photocrosslinkable and degradable polymers have found a broad range of applications as drug delivery vehicles, tissue engineering scaffolds, and in the fabrication of microdevices (J. Fisher, D. Dean, P. Engel, A. Mikos, ANN REV MATER RES 2001, 31, 171; K. Anseth, J. Burdick, MRS BULL 2002, 27, 130; D. J. Beebe, J. S. Moore, Q. Yu, R. H. Liu, M. L. Kraft, B. H. Jo, C. Devadoss, Proc Natl Acad Sci USA 2000, 97, 13488; each of which is incorporated herein by reference). The spatial and temporal control afforded during photoinitiated polymerizations has led to its use in a wide variety of fields including the field of biomaterials (J. Fisher, D. Dean, P. Engel, A. Mikos, ANN REV MATER RES 2001, 31, 171; K. Anseth, J. Burdick, MRS BULL 2002, 27, 130; each of which is incorporated herein by reference). For example, photocrosslinkable hydrogels are used for the delivery of cells to injured tissues (K. T. Nguyen, J. L. West, BIOMATERIALS 2002, 23, 4307; J. A. Burdick, K. S. Anseth, BIOMATERIALS 2002, 23, 4315; J. Leach, K. Bivens, C. Patrick, C. Schmidt, BIOTECHNOL BIOENG 2003, 82, 578; B. K. Mann, A. S. Gobin, A. T. Tsai, R. H. Schmedlen, J. L. West, BIOMATERIALS 2001, 22, 3045; K. Smeds, M. Grinstaff, J BIOMED MATER RES 2001, 54, 115; each of which is incorporated herein by reference), for the encapsulation and controlled delivery of biological molecules (J. WEST, J. HUBBELL, REACT POLYM 1995, 25, 139; J. A. Burdick, M. Ward, E. Liang, M. J. Young, R. Langer, BIOMATERIALS 2006, 27, 452; K. S. Anseth, A. T. Metters, S. J. Bryant, P. J. Martens, J. H. Elisseeff, C. N. Bowman, J Control Release 2002, 78, 199; each of which is incorporated herein by reference), and for controlled fluid flow and cell confinement in microfluidics (A. Khademhosseini, J. Yeh, S. Jon, G. Eng, K. Y. Suh, J. A. Burdick, R. Langer, Lab Chip 2004, 4, 425; D. T. Eddington, D. J. Beebe, Adv Drug Deliv Rev 2004, 56, 199; each of which is incorporated herein by reference). Additionally, highly crosslinked photopolymers are currently used in denistry (K. S. Anseth, S. M. Newman, C. N. Bowman, Advances in Polymer Science 1995, 122, 177; incorporated herein by reference) and are being developed as bone-replacement materials (K. S. Anseth, V. R. Shastri, R. Langer, Nat Biotechnol 1999, 17, 156; J. P. Fisher, T. A. Holland, D. Dean, P. S. Engel, A. G. Mikos, J Biomater Sci Polym Ed 2001, 12, 673; each of which is incorporated herein by reference) and for the fabrication of micro-devices (J. B. Hutchison, K. T. Haraldsson, B. T. Good, R. P. Sebra, N. Luo, K. S. Anseth, C. N. Bowman, Lab Chip 2004, 4, 658; incorporated herein by reference). Many of these applications are only possible due to the controlled nature of this type of polymerization. For example, photoinitiated control of polymerization allows for their application as injectable biomaterials (J. Elisseeff, K. Anseth, D. Sims, W. McIntosh, M. Randolph, R. Langer, Proc Natl Acad Sci USA 1999, 96, 3104; N. R. Luman, K. A. Smeds, M. W. Grinstaff, Chemistry 2003, 9, 5618; each of which is incorporated herein by reference) with a non-cytotoxic polymerization process (S. J. Bryant, C. R. Nuttelman, K. S. Anseth, J Biomater Sci Polym Ed 2000, 11, 439; incorporated herein by reference). Additionally, through use of masks and lasers, the spatial control of the polymerization process allows for unique patterning and construction of complex materials (V. A. Liu, S, N. Bhatia, Biomedical Microdevices 2002, 4, 257; incorporated herein by reference).
Numerous photopolymerizable and degradable materials have been developed, including polyanhydrides, poly(propylene fumarates), poly(ethylene glycol), and polysaccharides (K. Smeds, M. Grinstaff J BIOMED MATER RES 2001, 54, 115; K. S. Anseth, V. R. Shastri, R. Langer, Nat Biotechnol 1999, 17, 156; J. P. Fisher, T. A. Holland, D. Dean, P. S. Engel, A. G. Mikos, J Biomater Sci Polym Ed 2001, 12, 673; J. Elisseeff K. Anseth, D. Sims, W. McIntosh, M. Randolph, R. Langer, Proc Natl Acad Sci USA 1999, 96, 3104; each of which is incorporated herein by reference), all utilizing multiple reaction and purification steps for synthesis of the photopolymerizable precursors. Despite this work, it has proven challenging to predict specific desirable properties (e.g., degradation and mechanics) from known chemical and structural details of the network precursors.
The synthesis of multifunctional macromers that form these degradable networks commonly involves multiple functionalization and purification steps, which makes the development of large numbers of polymers with diverse properties difficult. In the search for polymers useful in drug delivery, specifically transfecting nucleic acids such as DNA and RNA, multiple libraries of poly(beta-amino esters) was prepared. These polymers are prepared by the conjugate addition of amines (e.g., primary amines, bis-secondary amines) to diacrylates. The properties of the resulting polyesters which contain tertiary amines can be adjusted by using different amines and diacrylate in the synthesis. For example, various tails on the amines or the linker between the diacrylates can be varied to achieve the desired properties of the resulting polymer. The ends of the resulting polymers may be controlled by adding an excess of amine or diacrylate to the reaction mixture. Given the biodegradable ester linkage in the resulting polymers, they are biodegradable.
There exists a continuing need for non-toxic, biodegradable, biocompatible materials with a variety of properties that are easily prepared efficiently and economically. Such materials would have several uses, including drug delivery, tissue engineering scaffolds, microdevices, biodegradable plastics, and biomaterials.